Inhibiting miR-27a and miR-142-5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway.
Alanine Transaminase
/ blood
Animals
Aspartate Aminotransferases
/ blood
Diet, High-Fat
/ adverse effects
Gene Expression Regulation
Hep G2 Cells
Humans
Lipid Metabolism
/ genetics
Male
Mice, Inbred C57BL
MicroRNAs
/ genetics
NF-E2-Related Factor 2
/ genetics
Non-alcoholic Fatty Liver Disease
/ etiology
Reactive Oxygen Species
Signal Transduction
/ genetics
NAFLD
Nrf2
lipogenesis
miR-142-5p
miR-27a
oxidative stress
Journal
IUBMB life
ISSN: 1521-6551
Titre abrégé: IUBMB Life
Pays: England
ID NLM: 100888706
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
30
11
2019
accepted:
16
12
2019
pubmed:
1
1
2020
medline:
15
4
2021
entrez:
1
1
2020
Statut:
ppublish
Résumé
The gene Nrf2 (nuclear factor-erythroid 2-related factor 2) is the most important regulator of the cellular antioxidant system and its dysregulation has a role in the etiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the association between Nrf2 targeted miRNAs (miR-27a, miR-142-5p, miR-153, and miR-128) with lipid accumulation in vitro and in vivo models of NAFLD. We used two in vivo and in vitro models of NAFLD. The expression of the genes and miRNAs was assessed by real-time PCR and the protein level was evaluated using western blot. To investigate the potential role of miRNAs in NAFLD, the inhibitors or mimics of the miR-27a and miR-142-5p were transfected into HepG2 cells. The mRNA and protein levels of Nrf2 were significantly decreased in the liver of high fat diet-fed mice as well as in HepG2 cells treated with high glucose (HG). Reduced expression of Nrf2 was associated with increased expression levels of miR-27a and miR-142-5p in both models of NAFLD. HG-induced triglyceride accumulation was attenuated by inhibition of miR-27a or miR-142-5p in HepG2 cells. Overexpression of miR-27a or miR-142-5p suppressed the expression of Nrf2 and its downstream antioxidant genes and increased production of reactive oxygen species, whereas inhibition of miR-27a or miR-142-5p reversed these effects. In conclusion, the data of this study may suggest that miR-27a and miR-142-5p are increased in NAFLD, where they suppress Nrf2 expression and contribute to the accumulation of lipids in the hepatocytes.
Substances chimiques
MIRN142 microRNA, human
0
MIRN27 microRNA, human
0
MicroRNAs
0
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
Reactive Oxygen Species
0
Aspartate Aminotransferases
EC 2.6.1.1
Alanine Transaminase
EC 2.6.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
361-372Informations de copyright
© 2019 International Union of Biochemistry and Molecular Biology.
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